PUBLICATION

A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription

Authors
Yi, C., Spitters, T.W., Al-Far, E.A.A., Wang, S., Xiong, T., Cai, S., Yan, X., Guan, K., Wagner, M., El-Armouche, A., Antos, C.L.
ID
ZDB-PUB-210409-18
Date
2021
Source
eLIFE   10: (Journal)
Registered Authors
Antos, Christopher
Keywords
developmental biology, zebrafish
MeSH Terms
  • Animal Fins/embryology
  • Animal Fins/growth & development
  • Animal Fins/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Calcineurin/genetics
  • Calcineurin/metabolism*
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Ion Channel Gating
  • Male
  • Membrane Potentials
  • Morphogenesis
  • Phosphorylation
  • Potassium/metabolism*
  • Potassium Channels, Tandem Pore Domain/genetics
  • Potassium Channels, Tandem Pore Domain/metabolism*
  • Protein Processing, Post-Translational
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcription, Genetic*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33830014 Full text @ Elife
Abstract
The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping